Pneumoproteins are associated with pulmonary function in HIV-infected persons
Autoři:
Diane Jeon aff001; Emily G. Chang aff002; Maggie McGing aff002; Marlena Hartman-Filson aff002; Mathew Sommers aff002; Eula Lewis aff003; John R. Balmes aff001; Daniela Moisi aff006; Michael M. Lederman aff006; Kristine A. Madsen aff004; Prescott G. Woodruff aff007; Peter W. Hunt aff008; Laurence Huang aff002;
Působiště autorů:
University of California Berkeley-University of California San Francisco Joint Medical Program, Berkeley, California, United States of America
aff001; HIV, ID and Global Medicine Division, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, California, United States of America
aff002; Department of Anesthesia and Perioperative Care, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, California, United States of America
aff003; School of Public Health, University of California Berkeley, Berkeley, California, United States of America
aff004; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, California, United States of America
aff005; Department of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
aff006; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
aff007; Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
aff008
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0223263
Souhrn
Background
COPD is a common HIV comorbidity, and HIV-infected individuals have a higher incidence and earlier onset of COPD compared to HIV-uninfected individuals. While the pathogenesis of HIV-associated COPD is largely unknown, chronic inflammation may contribute. Four pneumoproteins known to be markers of lung injury and inflammation have been associated with COPD in HIV-uninfected individuals: PARC/CCL-18, SP-D, CC-16, and sRAGE.
Objective
To determine whether these pneumoproteins are also associated with pulmonary function and COPD Assessment Test (CAT) scores in HIV-infected individuals.
Methods
Associations between plasma pneumoprotein levels and pulmonary function were determined in a cross-sectional study of otherwise healthy HIV-infected individuals enrolled between September 2016 and June 2017. Covariates included HIV-associated (antiretroviral therapy, CD4 count, and viral load) and COPD-associated (smoking and BMI) covariates.
Results
Among 65 participants, 78.5% were male, 50.8% had undetectable viral load, and 76.9% were ever-smokers. Mean post-bronchodilator FEV1/FVC was 0.71, and mean DLco%predicted was 61%. Higher PARC/CCL-18 was associated with lower DLco%predicted and higher CAT score. Higher CC-16 was associated with lower DLco%predicted and lower FVC%predicted.
Conclusions
This exploratory analysis is the first to characterize associations between these four pneumoproteins and pulmonary function in an HIV-infected cohort. Our findings suggest the pathogenesis of HIV-associated COPD may differ from that of non-HIV-associated COPD due to HIV-specific inflammatory changes affecting DLco. PARC/CCL-18 is associated with structural and functional pulmonary abnormalities and may be an important COPD biomarker candidate in HIV infection. Our study is a preliminary step toward finding clinically relevant COPD biomarkers in high-risk populations.
Klíčová slova:
Biomarkers – Chronic obstructive pulmonary disease – Inflammation – Inflammatory diseases – Pulmonary function – Smoking habits – Viral load
Zdroje
1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. 2014; 2163–2196.
2. Lozano R, Naghavi M, Foreman K, Lim SS, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380: 2095–128. doi: 10.1016/S0140-6736(12)61728-0 23245604
3. Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): A multicohort collaboration. Lancet. 2014;384: 241–248. doi: 10.1016/S0140-6736(14)60604-8 25042234
4. Crothers K, McGinnis K, Kleerup E, Wongtrakool C, Hoo GS, Kim J, et al. HIV infection is associated with reduced pulmonary diffusing capacity. J Acquir Immune Defic Syndr. 2013;64: 271–8. doi: 10.1097/QAI.0b013e3182a9215a 23979001
5. Gingo MR. MR, Balasubramani GK. GK, Rice TB. TB, Kingsley LL. c, Kleerup ECEC., Detels RR., et al. Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts. BMC Pulm Med. 2014;14: 75. doi: 10.1186/1471-2466-14-75 24884738
6. Drummond MB, Huang L, Diaz PT, Kirk GD, Kleerup EC, Morris A, et al. Factors associated with abnormal spirometry among HIV-infected individuals. Aids. 2015;29: 1691–1700. doi: 10.1097/QAD.0000000000000750 26372280
7. Drummond MB, Merlo CA, Astemborski J, Kalmin MM, Kisalu A, Mcdyer JF, et al. The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort. AIDS. 2013;27: 1303–11. doi: 10.1097/QAD.0b013e32835e395d 23299176
8. Drummond MB, Kirk GD, Astemborski J, Marshall MM, Mehta SH, McDyer JF, et al. Association between obstructive lung disease and markers of HIV infection in a high-risk cohort. Thorax. 2012;67: 309–14. doi: 10.1136/thoraxjnl-2011-200702 22090038
9. Fitzpatrick ME, Gingo MR, Kessinger C, Lucht L, Kleerup E, Greenblatt RM, et al. HIV infection is associated with diffusing capacity impairment in women. J Acquir Immune Defic Syndr. 2013;64: 284–8. doi: 10.1097/QAI.0b013e3182a9213a 23979000
10. Fitzpatrick ME, Singh V, Bertolet M, Lucht L, Kessinger C, Michel J, et al. Relationships of pulmonary function, inflammation, and T-cell activation and senescence in an HIV-infected cohort. AIDS. 2014;28: 2505–2515. doi: 10.1097/QAD.0000000000000471 25574956
11. Crothers K, Butt AA, Gibert CL, Rodriguez-Barradas MC, Crystal S, Justice AC. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest. 2006;130: 1326–1333. doi: 10.1378/chest.130.5.1326 17099007
12. Crothers K, Huang L, Goulet JL, Goetz MB, Brown ST, Rodriguez-Barradas MC, et al. HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era. Am J Respir Crit Care Med. 2011;183: 388–395. doi: 10.1164/rccm.201006-0836OC 20851926
13. George MP, Kannass M, Huang L, Sciurba FC, Morris A. Respiratory symptoms and airway obstruction in HIV-infected subjects in the HAART era. PLoS One. 2009;4: 1–7. doi: 10.1371/journal.pone.0006328 19621086
14. Gingo MR, George MP, Kessinger CJ, Lucht L, Rissler B, Weinman R, et al. Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era. Am J Respir Crit Care Med. 2010;182: 790–796. doi: 10.1164/rccm.200912-1858OC 20522793
15. Wheaton AG, Cunningham TJ, Ford ES, Croft JB. Employment and activity limitations among adults with chronic obstructive pulmonary disease—United States, 2013. MMWR Morb Mortal Wkly Rep. 2015;64: 289–295. Available: http://search.ebscohost.com/login.aspx?direct=true&db=rzh&AN=103778382&site=ehost-live 25811677
16. Doney B, Hnizdo E, Syamlal G, Kullman G, Burchfiel C, Martin CJ, et al. Prevalence of Chronic Obstructive Pulmonary Disease Among US Working Adults Aged 40 to 70 Years. J Occup Environ Med. 2014;56: 1088–1093. doi: 10.1097/JOM.0000000000000232 25285832
17. Morris A, George MP, Crothers K, Huang L, Lucht L, Kessinger C, et al. HIV and chronic obstructive pulmonary disease: is it worse and why? Proc Am Thorac Soc. 2011;8: 320–5. doi: 10.1513/pats.201006-045WR 21653535
18. Fitzpatrick M, Crothers K, Morris A. Future Directions. Clin Chest Med. 2013;34: 325–331. doi: 10.1016/j.ccm.2013.01.010 23702180
19. Gingo MR, Morris A, Crothers K. Human Immunodeficiency Virus–Associated Obstructive Lung Diseases. Clin Chest Med. 2013;34: 273–282. doi: 10.1016/j.ccm.2013.02.002 23702176
20. Drummond M, Kunisaki K, Huang L. Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs. Semin Respir Crit Care Med. 2016;37: 277–288. doi: 10.1055/s-0036-1578801 26974304
21. Deeks SG, Tracy R, Douek DC. Systemic Effects of Inflammation on Health during Chronic HIV Infection. Immunity. 2013;39: 633–645. doi: 10.1016/j.immuni.2013.10.001 24138880
22. Hunt PW. HIV and inflammation: Mechanisms and consequences. Curr HIV/AIDS Rep. 2012;9: 139–147. doi: 10.1007/s11904-012-0118-8 22528766
23. Deeks SG. HIV Infection, Inflammation, Immunosenescence, and Aging. Annu Rev Med. 2011;62: 141–155. doi: 10.1146/annurev-med-042909-093756 21090961
24. Fitzpatrick ME, Nouraie M, Gingo MR, Camp D, Kessinger CJ, Sincebaugh JB, et al. Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons. Aids. 2016; 1. doi: 10.1097/QAD.0000000000001092 26990629
25. Decramer M, Vestbo J. Chronic Obstructive Pulmonary Disease Updated 2016 Global Initiative for Chronic Obstructive L ung D isease. Gold. 2016; 1–44.
26. Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, et al. Changes in Forced Expiratory Volume in 1 Second over Time in COPD. N Engl J Med. 2011;365: 1184–1192. doi: 10.1056/NEJMoa1105482 21991892
27. Woodruff PG, Barr RG, Bleecker E, Christenson SA, Couper D, Curtis JL, et al. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. N Engl J Med. 2016;374: 1811–1821. doi: 10.1056/NEJMoa1505971 27168432
28. Faner R, Tal-Singer R, Riley JH, Celli B, Vestbo J, MacNee W, et al. Lessons from ECLIPSE: a review of COPD biomarkers. Thorax. 2014;69: 666–672. doi: 10.1136/thoraxjnl-2013-204778 24310110
29. Thomsen M, Ingebrigtsen TS, Marott JL, Dahl M, Lange P, Vestbo J, et al. Inflammatory Biomarkers and Exacerbations. J Am Med Assoc. 2013;309: 2353–2361. doi: 10.1001/jama.2013.5732 23757083
30. Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185: 1065–1072. doi: 10.1164/rccm.201110-1792OC 22427534
31. Cheng DT, Kim DK, Cockayne DA, Belousov A, Bitter H, Cho MH, et al. Systemic soluble receptor for advanced glycation endproducts is a biomarker of emphysema and associated with AGER genetic variants in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188: 948–957. doi: 10.1164/rccm.201302-0247OC 23947473
32. Park HY, Churg A, Wright JL, Li Y, Tam S, Man SFP, et al. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188: 1413–1419. doi: 10.1164/rccm.201305-0892OC 24245748
33. Lomas D a, Silverman EK, Edwards LD, Miller BE, Coxson HO, Tal-Singer R. Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort. Thorax. 2008;63: 1058–63. doi: 10.1136/thx.2008.102574 18757456
34. Lomas DA, Silverman EK, Edwards LD, Locantore NW, Miller BE, Horstman DH, et al. Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J. 2009;34: 95–102. doi: 10.1183/09031936.00156508 19164344
35. Sin DD, Miller BE, Duvoix A, Man SFP, Zhang X, Silverman EK, et al. Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183: 1187–1192. doi: 10.1164/rccm.201008-1220OC 21216880
36. Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009;34: 648–654. doi: 10.1183/09031936.00102509 19720809
37. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26: 319–38. doi: 10.1183/09031936.05.00034805 16055882
38. MacIntyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CPM, Brusasco V, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26: 720–735. doi: 10.1183/09031936.05.00034905 16204605
39. Hankinson IL, Odencrantz JR, Fedan KB. Spirometrie Reference Values from a Sample of the General U. S. Population. Am J Respir Crit Care Med. 1999;159: 179–187. doi: 10.1164/ajrccm.159.1.9712108 9872837
40. Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123: 659–64. doi: 10.1164/arrd.1981.123.6.659 7271065
41. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26: 948–968. doi: 10.1183/09031936.05.00035205 16264058
42. U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 2010. doi: 10.1037/e590462011-001
43. Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, et al. Persistent systemic inflammation is associated with poor clinical outcomes in copd: A novel phenotype. PLoS One. 2012;7. doi: 10.1371/journal.pone.0037483 22624038
44. Pinto-Plata V, Toso J, Lee K, Park D, Bilello J, Mullerova H, et al. Profiling serum biomarkers in patients with COPD: associations with clinical parameters. Thorax. 2007;62: 595–601. doi: 10.1136/thx.2006.064428 17356059
45. Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, et al. Decreased lung function and all-cause mortality in HIV-infected individuals. Ann Am Thorac Soc. 2018;15: 192–199. doi: 10.1513/AnnalsATS.201606-492OC 29313714
46. Schutyser E. Involvement of CC chemokine ligand 18 (CCL18) in normal and pathological processes. J Leukoc Biol. 2005;78: 14–26. doi: 10.1189/jlb.1204712 15784687
47. Hieshima K, Imai T, Baba M, Shoudai K, Ishizuka K, Nakagawa T, et al. A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes. J Immunol. 1997;159: 1140–9. Available: http://www.ncbi.nlm.nih.gov/pubmed/9233607 9233607
48. Atamas SP, Luzina IG, Choi J, Tsymbalyuk N, Carbonetti NH, Singh IS, et al. Pulmonary and Activation-Regulated Chemokine Stimulates Collagen Production in Lung Fibroblasts. Am J Respir Cell Mol Biol. 2003;29: 743–749. doi: 10.1165/rcmb.2003-0078OC 12805086
49. Pardo A, Smith KM, Abrams J, Coffman R, Bustos M, Mcclanahan TK, et al. CCL18 / DC-CK-1 / PARC up-regulation in hypersensitivity pneumonitis quantitative PCR and localized in lungs by in situ. 2001;70: 610–616.
50. Dilektasli AG, Cetinoglu ED, Uzaslan E, Budak F, Coskun F, Ursavas A, et al. Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization. Int J COPD. 2017;12: 199–208. doi: 10.2147/COPD.S118424 28115842
51. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity Index in Chronic Obstructive Pulmonary Disease. N Engl J Med. 2004;350: 1005–1012. doi: 10.1056/NEJMoa021322 14999112
52. Brune KA, Ferreira F, Mandke P, Chau E, Aggarwal NR, D’Alessio FR, et al. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation. PLoS One. 2016;11: e0149679. doi: 10.1371/journal.pone.0149679 26930653
53. Bernard A, Marchandise FX, Depelchin S, Lauwerys R, Sibille Y. Clara cell protein in serum and bronchoalveolar lavage. Eur Respir J. 1992;5: 1231–1238. Available: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1486970 1486970
54. Zemans RL, Jacobson S, Keene J, Kechris K, Miller BE, Tal-Singer R, et al. Multiple biomarkers predict disease severity, progression and mortality in COPD. Respir Res. 2017;18: 1–10. doi: 10.1186/s12931-016-0492-7
55. Brenchley JM, Douek DC. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 2008;1: 23–30. doi: 10.1038/mi.2007.1 19079157
56. Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, et al. Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. J Infect Dis. 2014;210: 1228–1238. doi: 10.1093/infdis/jiu238 24755434
57. Van Miert E, Dumont X, Bernard A. CC16 as a marker of lung epithelial hyperpermeability in an acute model of rats exposed to mainstream cigarette smoke. Toxicol Lett. 2005;159: 115–123. doi: 10.1016/j.toxlet.2005.05.007 16165332
58. Arjomandi M, Balmes JR, Frampton MW, Bromberg P, Rich DQ, Stark P, et al. Respiratory Responses to Ozone Exposure: The Multicenter Ozone Study in oldEr Subjects (MOSES). Am J Respir Crit Care Med. 2017; rccm.201708-1613OC. doi: 10.1164/rccm.201708-1613OC 29232153
59. Buendía-Roldán I, Ruiz V, Sierra P, Montes E, Ramírez R, Vega A, et al. Increased expression of CC16 in patients with idiopathic pulmonary fibrosis. PLoS One. 2016;11: 1–11. doi: 10.1371/journal.pone.0168552 27977812
60. Hasegawa M, Fujimoto M, Hamaguchi Y, Matsushita T, Inoue K, Sato S, et al. Use of serum Clara cell 16-kDa (CC16) Levels as a potential indicator of active pulmonary fibrosis in systemic sclerosis. J Rheumatol. 2011;38: 877–884. doi: 10.3899/jrheum.100591 21239758
61. Jorens PG, Sibille Y, Goulding NJ, van Overveld FJ, Herman AG, Bossaert L, et al. Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury. Eur Respir J. 1995;8: 1647–53. Available: http://www.ncbi.nlm.nih.gov/pubmed/8586116 doi: 10.1183/09031936.95.08101647 8586116
62. Broeckaert F, Arsalane K, Hermans C, Bergamaschi E, Brustolin A, Mutti A, et al. Serum Clara cell protein: A sensitive biomaker of increased lung epithelium permeability caused by ambient ozone. Environ Health Perspect. 2000;108: 533–537. doi: 10.1289/ehp.00108533 10856027
63. Yonchuk JG, Silverman EK, Bowler RP, Agustí A, Lomas DA, Miller BE, et al. Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung. Am J Respir Crit Care Med. 2015;192: 785–792. doi: 10.1164/rccm.201501-0137PP 26132989
64. Miniati M, Monti S, Basta G, Cocci F, Fornai E, Bottai M. Soluble receptor for advanced glycation end products in COPD: relationship with emphysema and chronic cor pulmonale: a case-control study. Respir Res. 2011;12: 37. doi: 10.1186/1465-9921-12-37 21450080
65. Woodruff PG, Agusti A, Roche N, Singh D, Martinez FJ. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management. Lancet. 2015;385: 1789–1798. doi: 10.1016/S0140-6736(15)60693-6 25943943
66. Rennard SI, Locantore N, Delafont B, Tal-Singer R, Silverman EK, Vestbo J, et al. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann Am Thorac Soc. 2015;12: 303–312. doi: 10.1513/AnnalsATS.201403-125OC 25642832
67. Morris A, Alexander T, Radhi S, Lucht L, Sciurba FC, Kolls JK, et al. Airway obstruction is increased in Pneumocystis-colonized human immunodeficiency virus-infected outpatients. J Clin Microbiol. 2009;47: 3773–3776. doi: 10.1128/JCM.01712-09 19759224
68. Liu JCY, Leung JM, Ngan DA, Nashta NF, Guillemi S, Harris M, et al. Absolute Leukocyte Telomere Length in HIV-Infected and Uninfected Individuals: Evidence of Accelerated Cell Senescence in HIV-Associated Chronic Obstructive Pulmonary Disease. PLoS One. 2015;10: e0124426. doi: 10.1371/journal.pone.0124426 25885433
69. Sampériz G, Guerrero D, López M, Valera J, Iglesias A, Ríos Á, et al. Prevalence of and risk factors for pulmonary abnormalities in HIV-infected patients treated with antiretroviral therapy. HIV Med. 2014;15: 321–329. doi: 10.1111/hiv.12117 24314004
70. Agusti A, Calverley PMA, Celli B, Coxson HO, Edwards LD, Lomas D a, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11: 122. doi: 10.1186/1465-9921-11-122 20831787
71. Jones PW, Brusselle G, Dal Negro RW, Ferrer M, Kardos P, Levy ML, et al. Properties of the COPD assessment test in a cross-sectional European study. Eur Respir J. 2011;38: 29–35. doi: 10.1183/09031936.00177210 21565915
72. Jones PW. Expert guidance on frequently asked questions Introducing the COPD Assessment Test (CAT). 2009; 1–8.
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